This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Microwave assisted organic synthesis (MAOS) is being employed to synthesize cytotoxic arylphosphonium salts (APS). APS exhibit structure-activity relationships as antibiotics, in DNA binding, enzyme inhibition and against malignant cells. They cross cell membranes and accumulate in mitochondria of malignant cells. They deliver DNA alkylating agents into cancer cells, inhibit acetylcholinesterase, bovine serum amine oxidase, protein kinase C and HIV integrase. Among possible consequences are disruption of metabolism and cell division from blocked enzymes and interference with replication. A report of the latter with student co-authors has been published. APS effects in DNA melting, electrophoresis, and isothermal titration calorimetry are being studied. A student co-authored article on in silico APS-estrogen-receptor binding has been published. We will do further experiments at RIC and Brown EPSCoR on toxicity mechanisms of APS. We have synthesized new APS-fluorescent conjugates and observed their uptake by live cells. We have prepared APS polymers and graft polymers that are antibiotic. AutoDock, HyperChem and eHitsLightning will and are being used to calculate APS-DNA interactions. Polymeric APS will be tested further for antibacterial activity for potential use in medical plastics. New APS will be screened for DNA-replication toxicity. A crystallization project to make complexes for X-ray structure determination is underway and crystals have been isolated from DNA-APS hanging-drop experiments. Solid-state polypeptide synthesis will provide polypeptides for conjugates to APS and for DNA complexing studies. Triphenyltriazoles will be synthesized and incorporated into polypeptide co-polymers to make antibiotic and/or biodegradable macromolecules.